Evaluation of Blink Tears and Systane Concomitant With Restasis for the Treatment of Dry Eye Symptoms: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Evaluation of Blink Tears and Systane Concomitant With Restasis for the Treatment of Dry Eye Symptoms (NCT00565669), a randomized na study. The primary outcome is Change in Schirmer's Scores.

2. Clinical Question

3. Trial Design

The registry describes a randomized, parallel-group trial with no masking. The recorded enrollment is 20, and the study status is completed. Its listed condition is Dry Eye Syndrome. The sponsor is the Medical University of South Carolina. The recorded start is 2007-10 and primary completion is 2008-10.

The study’s stated purpose was to evaluate Blink Tears and Systane used concomitantly with topical cyclosporine for dry eye. Cyclosporin A Restasis®, Blink tears, and Systane appear in the intervention list. The primary outcome results are organized into a Blink Tears arm and a Systane arm. The record does not include descriptions of either arm, so the precise regimen, treatment schedule, and any other differences between groups are not reported in the registry record.

Random allocation means that assignment is intended to use chance rather than a researcher’s choice. The record does not report how the random sequence was generated, whether assignment was concealed until enrollment, or whether any restrictions were used in randomization. Those details should not be inferred from the word “randomized.” The study is listed as unmasked, but the registry does not say which people involved in care, measurement, or analysis knew the assignments.

A parallel design assigns participants to one group for the comparison rather than describing a crossover between treatments. The posted outcome entry reports a group mean change and its standard error for each arm. It does not report a formal between-group estimate or a test of the difference. No protocol rationale for enrollment, detailed statistical plan, or account of trial conduct beyond the registry fields is reported in the registry record.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as Change in Schirmer's Scores, measured over baseline to 3 months.

The primary endpoint is change in Schirmer’s score from baseline to 3 months. The calculation is defined as the 3-month score minus the baseline score. Schirmer’s test measures tear production using a score on a scale; the registry describes a minimum of 0 and a highest value of 35 mm. It states that a score above 15 mm is normal and a score less than 5 indicates severe dry eyes.

Change is useful because it expresses how a participant’s measured score moved from their own baseline during follow-up. Under the registry’s definition, a positive change means improvement, zero means no change, and a negative change means a decrease in tears. The outcome is continuous, so the posted arm results are means rather than counts of participants in categories.

The registry reports the timeframe as baseline to 3 months. It does not report the number of participants with an observed endpoint separately from the arm sample sizes, nor does it describe how missing measurements were handled. A mean change describes the group’s average observed change; by itself, it does not show the range of individual responses, whether change was clinically important, or whether the groups differed statistically.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is continuous, and the registry reports an arm-specific mean change with a standard error. A mean is a measure of the center of a set of measurements. Here it summarizes the average change in score within each arm. Because the endpoint is defined as the 3-month score minus the baseline score, the sign carries direction: positive values represent increases, while negative values represent decreases.

A standard error describes the precision of an estimated mean. In general, it reflects how much the mean estimate would vary across repeated samples under the assumptions of the analysis. It is not a direct description of how widely individual participants’ scores varied. The registry labels the reported dispersion as standard error, but does not provide a confidence interval for either mean or for a contrast between arms.

A confidence interval is a range of estimates constructed by a specified method. It can help readers judge both the direction and precision of an estimated effect. For a randomized comparison, the most relevant interval would ordinarily concern the between-arm contrast, because that targets the difference in average change between assigned groups. No such contrast or confidence interval is reported in the registry record. The reported arm means and standard errors alone do not establish the statistical uncertainty of that comparison without additional assumptions and a defined analysis.

A hypothesis test for a between-group difference would address whether the observed data are inconsistent with a specified null hypothesis under the chosen model. A p-value would not measure the probability that a treatment effect is true, nor would it determine whether a difference matters clinically. In this record, no primary comparison test or p-value is posted. Therefore, the evidence should not be described as statistically significant or not statistically significant on the basis of the available registry results.

The registry marks the continuous two-arm comparison as not estimable from the posted values. This means that a recalculated comparison is not available as a simple unadjusted calculation based on the posted summaries. It is distinct from the sponsor’s own analysis: no sponsor analysis is posted in the outcome entry. There is no reported sponsor result that can be used to resolve the missing comparison.

Randomization can support a causal comparison when assignment is implemented as planned, outcomes are measured appropriately, and the analysis preserves the randomized comparison. The word “randomized” alone does not describe sequence generation, concealment, adherence, follow-up, or analysis population. Those details are not reported in the registry record. The no-masking designation also matters when considering possible influences on care or assessment, but the record does not specify who knew assignments or how outcome measurement was conducted.

The posted outcome is a change score. In general, analysis of change can be affected by baseline values, measurement variability, and the relationship between baseline and follow-up measurements. An analysis that adjusts for baseline may answer a related question with different precision from a simple comparison of change scores. The registry does not report whether the result was adjusted, what model was used, or whether any assumptions were checked. No particular analysis should be inferred.

Continuous outcomes can sometimes have a distribution with more variability than a simple model expects. Over-dispersion, in general, means that observed variability exceeds what a model assumes; if present and unaccounted for, uncertainty estimates can be too small. The registry does not provide enough distributional information to assess this issue or report a model that would make it relevant. Given the small arm sizes reported, the summaries also cannot show whether the observed changes were approximately symmetric or influenced by individual values. These are general considerations, not claims about the data in this trial.

The registry includes a sample-size planning illustration based on the observed effect, with a two-sided significance level of 0.05, equal allocation, and a normal approximation; the target effect is described as a stated fraction of the observed effect. These are planning assumptions, not evidence about the original design. Any resulting sample-size values are illustrations for future planning, not observed power and not a retrospective measure of whether the trial could detect an effect. The record does not report the trial’s own sample-size justification, target effect, or design calculation.

In general, power is a planning property tied to a specified effect, variability, test, and sample size. Calculating “observed power” from the trial’s estimated effect would not resolve the uncertainty in the reported result; confidence intervals and a well-described analysis are more informative. The record does not provide a planned analysis, interim analysis plan, or details about adjustment for multiple testing. These omissions leave the analytic context incomplete.

The record lists one primary outcome measure and no secondary outcome results. It does not describe whether multiple outcomes or time points were prespecified elsewhere, whether any analyses were omitted, or whether analytic choices were made before results were reviewed. Such details are not reported in the registry record. The appropriate reading is therefore limited to the posted descriptive means and their reported standard errors, without attributing an unreported model or testing procedure to the study.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("Blink Tears", "Systane")
n   <- c(11, 9)
m   <- c(-0.3, -1.06)
sp  <- c(2.82, 4.17)
sd  <- sp * sqrt(n)      # standard errors converted to SDs
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Blink Tears  11  -0.300  9.353  -6.583  5.983
CARM  Systane  9  -1.060  12.510  -10.676  8.556

11. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary outcome measure, change in Schirmer’s score from baseline to 3 months, and no secondary outcome results. It does not report a multiplicity strategy or explain whether other outcomes, time points, or subgroup analyses were planned. When several statistical hypotheses are tested, multiplicity can increase the chance of at least one apparently notable finding by chance. In general, a prespecified testing strategy or adjustment can address that issue, but the record does not say whether either was used. There is no basis to infer that the study had no other planned analyses simply because none are posted.

Missing-data handling is not described. The record gives arm sizes for the outcome summaries but does not report how many participants had usable measurements at each time point, whether any values were missing, or why they might be missing. It does not state whether participants were analyzed in their assigned groups, whether observations were excluded, or whether missing outcomes were imputed. These analysis-population and missing-data details are not reported in the registry record.

Such omissions matter because complete-case summaries may represent a selected subset if outcome availability is related to participants’ condition or response. Imputation and model-based methods also depend on assumptions that should be described. These are general statistical considerations, not evidence that missingness occurred in this trial. Without the relevant details, readers cannot determine how robust the reported means are to missing outcomes or how closely the analysis preserves random assignment.

The registry does not report a statistical analysis plan, interim analyses, or methods for handling multiple testing. These features should not be guessed. The posted results support a descriptive account of the primary endpoint, but do not allow a full assessment of prespecification, analysis population, or missing-data sensitivity.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

The registry’s serious adverse event entry reports 0 affected among 11 at risk in the group labeled “Blink Years,” and 0 affected among 9 at risk in the Systane group. The first label differs from the efficacy arm name Blink Tears; the registry record does not explain that discrepancy. The same adverse-event entry reports 0 other affected participants among 11 at risk in the first group and 0 among 9 at risk in the Systane group.

These are counts recorded during the registry’s safety reporting, not estimates that an event is impossible. A zero count means that no affected participants were recorded in that entry; it does not establish that no events could occur or that the groups have equal safety. With limited numbers of participants, rare events may not appear during observation. The record does not provide event definitions, observation time for safety, or detailed ascertainment procedures.

Deaths are listed as null rather than as a numerical count. Deaths are therefore not reported in the registry record, and null should not be interpreted as zero. The registry lists no serious-event terms. These safety summaries should be read as registry reporting, not as a complete safety assessment or a basis for medical decisions.

13. What the Result Does, and Does Not, Mean

The record contributes descriptive information about a randomized comparison of Blink Tears and Systane in people with Dry Eye Syndrome. The primary endpoint is change in Schirmer’s score from baseline to 3 months. The posted mean changes are negative in both arms: -0.3 for Blink Tears and -1.06 for Systane. Their reported standard errors are 2.82 and 4.17, respectively. Those values describe the reported arm summaries and their estimated precision as means.

They do not show the distribution of individual changes, identify how many participants improved or worsened, or establish the difference between the assigned groups. No formal two-arm analysis, confidence interval, or p-value for the primary comparison appears in the registry record. The record also does not report how missing outcome data were handled or which participants were included in the analysis. These absences prevent a complete evaluation of the comparative result.

The negative group means indicate that the average change reported in each arm was below baseline according to the endpoint’s stated sign convention. They do not establish that every participant experienced a decrease, and they do not by themselves indicate whether a change was important to participants. The registry’s reference points for the score describe the scale, but no threshold for a meaningful change is reported.

The trial’s stated purpose involved Blink Tears and Systane used concomitantly with topical cyclosporine, but the arm descriptions are blank. The record does not provide enough treatment detail to determine the exact regimen represented by each outcome group. It also does not report baseline scores, adherence, or other clinical context that could clarify the observed changes.

Accordingly, the results should not be taken as proof that either product is better, worse, effective, or ineffective. The record supports a narrow reading of the posted outcome summaries and safety counts. A stronger comparative conclusion would require a clearly reported analysis and further trial details that are not reported in the registry record.

14. Why This Trial Matters Statistically

This trial is statistically notable for the gap between a randomized design and the limited comparative analysis available in the registry. Randomization is intended to make treatment groups comparable on average, but readers need the analysis that uses that assignment to assess the primary question. Here, separate arm means and standard errors are posted, while a formal between-arm estimate is not. The distinction helps prevent descriptive summaries from being mistaken for evidence of a tested difference.

The endpoint also illustrates why direction, precision, and comparison are separate ideas. The sign of each mean change indicates the direction of the reported group average under the registry’s definition. The standard error conveys precision of the mean estimate. Neither statistic alone answers whether the arms differ. A confidence interval or test for the contrast would address that comparative uncertainty, but neither is reported.

The small arm sizes in the posted results make completeness of reporting especially important: readers need to know who contributed measurements, how missing data were handled, and what analysis was prespecified. Those details are not reported in the registry record. This does not establish a flaw in how the trial was conducted; it limits what can be independently assessed from the posted information.

The safety entry provides another useful statistical lesson. Zero recorded events are counts, not proof of zero risk. The interpretation depends on the number observed, the period and methods of ascertainment, and the kinds of events included. Some of those details are not reported, and deaths are not given as a numerical count.

Finally, the planning illustration based on the observed effect should be kept separate from the trial’s original design. Planning values can help explore assumptions for future work, but they are not observed power and do not replace a reported effect estimate with uncertainty. The record does not report the original sample-size rationale. Clear distinction among design, descriptive results, comparative inference, and planning assumptions is central to reading this study responsibly.

15. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The registry outcome record is sparse in several respects that limit interpretation of this particular trial. Arm descriptions are blank, even though the stated purpose refers to Blink Tears and Systane used concomitantly with topical cyclosporine. The record therefore does not specify the treatment schedule, duration of use beyond the endpoint timeframe, or other components of the regimens. It does not show whether the groups differed only by the lubricant named in the outcome entry.

Participant eligibility criteria and baseline characteristics are not included in the posted outcome information. The record names Dry Eye Syndrome, but does not show the starting Schirmer’s scores or other clinical features that could help describe the enrolled population. The outcome timeframe is given as baseline to 3 months, but follow-up completeness and measurement procedures are not described.

For the primary endpoint, the registry supplies arm means and standard errors but no formal comparison, interval estimate, or p-value. It also does not report individual outcome distributions, numbers with available measurements at each time point, or a missing-data approach. The intended analysis population and any adjustment for baseline or other variables are not reported in the registry record. These omissions prevent an independent assessment of the primary comparative question.

The randomization method and allocation concealment are not described, and the record states that masking was absent without specifying who knew assignments. No statistical analysis plan, sample-size justification, interim analysis information, or multiplicity approach is reported. The adverse-event group label “Blink Years” differs from the efficacy label Blink Tears, and the record does not explain the difference. Deaths are not reported as a numerical count. These limitations concern what the registry record allows readers to assess; they do not establish that a particular procedure was or was not followed.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Evaluation of Blink Tears and Systane Concomitant With Restasis for the Treatment of Dry Eye Symptoms — NCT00565669.
• Registry record last updated 2018-11-07; status last verified 2018-10.
• Results first posted 2018-11-07.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

19. Record Summary

NCT00565669 is a completed, randomized, parallel-group, unmasked trial sponsored by the Medical University of South Carolina. The registry lists Dry Eye Syndrome and enrollment of 20. Its stated purpose was to evaluate Blink Tears and Systane used concomitantly with topical cyclosporine.

The primary endpoint is change in Schirmer’s score from baseline to 3 months. The registry posts mean changes of -0.3 for Blink Tears and -1.06 for Systane, with standard errors of 2.82 and 4.17 and arm sizes of 11 and 9. It does not report a formal two-arm analysis of this outcome.

The safety entry records zero serious and zero other affected participants in each listed group. Deaths are not reported as a numerical count. Treatment details, missing-data handling, analysis populations, and the trial’s statistical plan are not reported in the registry record.